Method of using diketopiperazines and composition containing them
View Patent ↗The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R 1 and R 2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.
1. A pharmaceutical composition formulated as a liquid suspension for oral administration consisting essentially of a diketopiperazine having the formula:
wherein:
R 1 is —CH 2 COR 3 , or —CH 2 CH 2 COR 3 ,
R 2 is the side chain of an amino acid selected from the group consisting of alanine, leucine, and norvaline, and
R 3 is —OH or —NH 2 ; or
a physiologically-acceptable salt thereof; and
a suspending agent selected from the group consisting of ethoxylated isostearyl alcohols, polyoxyethylene sorbitol, sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, tragacanth, and mixtures thereof.
2. The pharmaceutical composition of claim 1 wherein R 2 is the side chain of alanine.
3. The pharmaceutical composition of claim 1 or 2 wherein R 3 is —OH.
4. The pharmaceutical composition of claim 3 wherein R 1 is —CH 2 COOH.
5. The pharmaceutical composition of claim 1 wherein R 2 is the side chain of leucine.
6. The pharmaceutical composition of claim 1 wherein R 2 is the side chain of norvaline.
7. The pharmaceutical composition of claim 1 wherein R 3 is NH 2 .